Automated DNA testing will reduce the costs of molecular genetic technology for clinical and research applications. Using manual methods, we have shown that genotypic analyses can provide rapid and accurate confirmation in the Texas neonatal hemoglobinopathy screening program. We propose an automated strategy based on allele specific cleavage of a PCR-amplified product anchored to the well of a microtiter plate. While this methodology would have broad clinical application for diagnosis of genetic and infectious diseases, we have targeted medium chain acyl-CoA dehydrogenase (MCAD) deficiency and sickle cell disease for the initial application. MCAD deficiency is associated with sudden infant death syndrome (SIDS) in the untreated child; treatment is simple, inexpensive and effective. Improved diagnostic confirmation of sickle cell disease and other hemoglobinopathies will facilitate initiation of penicillin prophylaxis to reduce death from sepsis. Newborn screening involves a test for each disorder in the screening program for every liveborn child: more than 300,000/year in Texas and about 4 million/year in the USA. MCAD screening on every neonate, hemoglobinopathy confirmatory testing and expansion to the other disorders will result in a significant reduction in morbidity and mortality. Application of this automated technology to basic research will improve the cost-effectiveness of genetic analyses for laboratory investigations in prokaryotic and eukaryotic systems.